Potentiation of a novel palladium (II) complex lethality with bee venom on the human T-cell acute lymphoblastic leukemia cell line (MOLT-4)

Zahra Safaeinejad,Zahra Nazari,Mohammad Nabiuni

doi:10.1186/1678-9199-19-25

Zahra Safaeinejad, Zahra Nazari + Show 1 more

Open Access

https://doi.org/10.1186/1678-9199-19-25

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Abstract

BackgroundAlthough honeybee venom (BV) has been reported to induce apoptosis in different types of cancerous cells, its synergistic effects with customary anti-cancer drugs remain largely unknown. In the present study, we evaluated the cytotoxic effect of BV alone (as a natural product) and the synergistic cytological effects of this component in combination with [Pd (bpy) (Pi-Pydtc)]NO3 – a novel palladium complex on human T-cell lymphoblastic leukemia cells. To investigate the cytotoxic effect of the BV alone and in combination with palladium complex on MOLT-4 cells MTT assay was performed. In order to determine the apoptotic effects of BV separately and in combination with Pd (II) complex on these cells and its ability to induce apoptosis, morphological examination, flowcytometric analysis and caspase-3 colorimetric assay were done.ResultsWe found that BV induced morphological changes, namely nuclear shrinkage, and inhibited MOLT-4 cell proliferation; both effects were dose- and time-dependent. Flow cytometry by Annexin-V antibody demonstrated that BV induced apoptosis in MOLT-4 cells. Furthermore, BV induced apoptosis independently of caspase-3 in these cells. In addition, we proved a clear synergistic effect of BV on [Pd (bpy) (Pi-Pydtc)]NO3. The apoptotic pathway activated by BV in combination with Pd complex was caspase-3-dependent.ConclusionsThese observations provide an explanation for the anti-proliferative properties of BV, and suggest that this agent may be useful for treating lymphoblastic leukemia alone or in combination with chemotherapy drugs pending further investigations on animal models as preclinical tests.

Highlights

Honeybee venom (BV) has been reported to induce apoptosis in different types of cancerous cells, its synergistic effects with customary anti-cancer drugs remain largely unknown
MTT cytotoxicity assay In order to determine the cytotoxic effects of Background: Although honeybee venom (BV) separately and in combination with Pd (II) complex on the MOLT-4 cells, cell viability was tested by MTT (3[4, 5-dimethylthiozol-2-yl]-2,5-diphenyl tetrazolium bromide) assay
Cell viability assay In order to determine the optimal dose and time of cytotoxic effect of BV alone and in combination with this novel Pd (II) complex on MOLT-4 cells, an MTT assay was performed

Summary

Introduction

Honeybee venom (BV) has been reported to induce apoptosis in different types of cancerous cells, its synergistic effects with customary anti-cancer drugs remain largely unknown. The dry venom has a very complex mixture of such active peptides as melittin, apamin and adolapine, enzymes including hyaluronidase and phospholipase A2, biologically active amines such as histamine and epinephrine as well as non-peptide components with numerous medicinal properties [2]. A hemolytic and strong cardiotoxic peptide, is the major active ingredient of BV. This main constituent of bee venom has been reported to induce apoptosis, and to produce anti-tumor effects [3,4]. The cytotoxic effects mediated through the activation of PLA2 by melittin have been suggested to be the critical mechanism for the anti-cancer activity of BV [12]

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